CD19, immunoglobulin level, and varied anti-cytokine autoantibodies underline dichotomous susceptibility to types of infection in patients with thymomas

Objectives: Increased susceptibility to infections is observed in patients with thymomas. These have been invariably attributed to Good syndrome with hypogammaglobulinemia, but there is noticeable heterogeneity in clinical presentation. We clinically and immunophenotypically characterized the infective susceptibilities encountered in these patients. Methods: Of thymoma patients recruited from Singapore and South Korea, their infection types were correlated against immunological parameters, including IgG, IgM, IgA, CD19+ B cells, and CD4+ T cells, and the presence of neutralizing anti-cytokine autoantibodies using direct ELISA. Lymphocyte subset immunophenotyping was performed. Ascertainment of immune signaling pathway disruption was through serum switch experiments. Respective immune signal outputs were probed using Western blotting. Results: infections. These patients had low immunoglobulins and CD19+ B cells. The second group of six patients (40%) had difficult-to-treat non-tuberculous mycobacterium (NTM) or invasive bacterial or fungal infections. They had normal immunoglobulins levels and possessed autoantibodies against interleukin (IL-)-12, IL--23, or interferon-alpha (IFN-α), which consisted of anti-IFN-α2 and anti-IFN-ω subtypes. The autoantibodies consisted of a heterogeneous spread across IgG1 to IgG4 subclasses. These anti-IL--12, anti-IL--23, and anti-IFN-α autoantibodies were neutralizing and compromised various phosphorylated-STAT signaling pathways that are critical in host anti-pathogen response. Conclusions: The dichotomy of infective manifestations (viral/PJP versus NTM/invasive bacteria/fungal) underlies distinct and novel immune susceptibility beyond the classic Good syndrome label in thymoma patients, with implications for different approaches to clinical management.